Lipoproteins are high molecular weight particles that are primarily responsible for lipid transport, namely of triglycerides and cholesterol in the form of cholesteryl esters, through the plasma. Five major classes of naturally-occurring lipoproteins are known to circulate in plasma, each differing in lipid composition, apoprotein composition, density, size, and electrophoretic mobility.
Each lipoprotein particle is composed of a non-polar core region, a surrounding phospholipid surface coating containing small amounts of cholesterol, and exposed at the surface, apoproteins responsible for binding to receptors on cell membranes and directing the lipoprotein carrier to its intended site of metabolism.
At least ten different apoprotein molecules have been identified, and each class of lipoprotein particle contains a specific apoprotein (also referred to as apolipoproteins) or combination of apoproteins embedded in its surface (Harrison). These apoproteins are encoded by genes localized to sites on chromosomes 1, 2, 6, 11, and 19, and mutations thereof are thought to play a role in atherogenesis.
The major classes of lipoproteins found in human plasma include chylomicrons and chylomicron remnant particles, VLDL (very low density lipoprotein), IDL (intermediate density lipoprotein), LDL (low density lipoprotein), and HDL (high density lipoprotein).
Chylomicrons contain a hydrophobic core primarily composed of dietary triglycerides and contain several apoproteins including AI, AII, B48, CI, CII, CIII, and E. VLDL contains a core of endogenous triglycerides synthesized in the liver, in addition to apoproteins B48, CI, CII, CIII, and E. IDL particles are composed of lipids including cholesteryl esters and triglycerides and contain apoproteins B100, CIII, and E. A fourth class of lipoprotein, LDL, possesses a core composed almost entirely of cholesteryl esters and has a surface coat containing only apo B100. About three-fourths of the total cholesterol in normal human plasma is contained within LDL particles. A fifth class of lipoprotein, HDL, also contains cholesteryl esters and possesses a surface coating which includes AI and AII apoproteins. A detailed description of the major classes of human lipoproteins and their function in lipid transport is provided in Harrison (Harrison, 1991).
In addition to the major classes of lipoproteins, a lipoprotein-like particle, Lp(a), has been identified and shown to bear a strong resemblance to both lipoprotein and plasminogen. Its protein components include apo B100 linked to apo (a) via a disulfide bridge. Although a relationship has not been clearly established, the structural resemblance of the lipoprotein-like Lp(a) particle to plasminogen is thought to provide a link between lipids, the clotting system, and atherogenesis.
HDL has been shown to be associated with a protective effect against atherosclerosis in humans (Miller, 1975; Blankenhorn, 1987). It has been hypothesized that HDL exerts its protective effect by the reverse transport of excess cholesterol from peripheral tissues to the liver (Bailey, 1965; Glomset, 1968). However, in regard to its role in anti-atherogenesis, the mechanisms of HDL uptake of cholesterol and delivery to the liver remain an issue of debate (Bisgaier, 1988).
In studies in rats, the vast majority of IDL is shown to be rapidly cleared by the liver. The mechanism of IDL uptake is not clearly understood, although it appears to involve a receptor-mediated process (Noel, 1983).
Numerous studies have been undertaken to elucidate the specific mechanisms of lipid uptake by lipoproteins, the role of lipoproteins in atherogenesis, additional physiological roles of lipoproteins, the identification of lipoprotein receptors responsible for cell surface binding, and the like. The findings resulting from such studies are often inconclusive due to the complex nature of lipoproteins and the accompanying complexity of the human lipid transport system, and are often derived from in-vitro studies or are based on animal models.